Crohn's Disease and Ulcerative Colitis (UC) are Inflammatory Bowel Diseases of unknown etiology. The exact pathogenesis is still unknown. One complication of UC is an increased risk for the development of colorectal cancer. The molecular basis of UC-associated cancer is poorly understood. Some of the genetic alterations include mutations of the K-ras oncogene, and of p53 and APC tumor suppressor genes. Dysplasia, a cytological and architectural alteration of the colon mucosa, is currently used as the sole marker of cancer risk. The objective of these studies is to identify early biomarkers that could be used for the detection of cancer development in UC patients. The central hypothesis of this proposal is that mutations in p53, K-ras and APC genes promote the formation of malignant cells that can result in tumors in UC-associated cancer. The specific aims of the proposed plan are to: 1) develop a new model of UC-associated cancer; 2) investigate gene mutations of p53, K-ras and APC during the transition of colitis to dysplasia; 3) correlate the histologic and macroscopic results with the molecular alterations of the genes under study. These findings may eventually provide a molecular tool for improved diagnosis of cancer in UC patients. [unreadable] [unreadable] [unreadable]